Serum Concentrations Of Metabolites Research Articles

Effects of vitamin E and selenium on thyroid status, adrenocorticotropin hormone, and blood serum metabolite and mineral concentrations of Japanese quails reared under heat stress (34°C)

AbstractThis study was conducted to determine the effects of vitamin E and selenium (Se) on triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), adrenocorticotropin hormone (ACTH), and serum glucose, urea, triglyceride, cholesterol, Ca, P, Na, and K concentrations of Japanese quails reared under heat stress (34°C). One‐hundred twenty 10‐day‐old Japanese quails were randomly assigned to four treatment groups with three replicates of 10 birds each. The birds with a 2 × 2 factorial design received either two levels of vitamin E (125 and 250 mg/kg of diet) or two levels of selenium (0.1 and 0.2 mg/kg of diet). Greater dietary vitamin E and selenium inclusions resulted in a greater (P = 0.001) serum T3, T4, and TSH, but lower (P = 0.001) ACTH concentrations. No interactions between vitamin E and selenium were detected (P ≥ 0.11) for serum concentrations of T3, T4, TSH, and ACTH. Serum glucose, urea, triglyceride, and cholesterol concentrations decreased (P = 0.001), whereas protein concentrations increased (P = 0.001) when both dietary vitamin E and selenium increased. Serum albumin concentrations increased (P = 0.001) with greater dietary vitamin E but did not change with dietary selenium (P = 0.16). No interactions on any blood metabolites were detected (P ≥ 0.11). Serum activities of serum glutamic oxalate transaminase and serum glutamic pyruvate transaminase were not influenced by dietary vitamin E or selenium (P ≥ 0.42). However, serum activity of alkaline phosphatase increased (P = 0.001) with both increasing dietary vitamin E and selenium. There were no interactions detected for the serum enzyme activities (P ≥ 0.09). Increasing both dietary vitamin E and selenium caused an increase in serum concentrations of Ca, P, and K (P = 0.001), but a decrease in serum concentrations of Na (P = 0.001). No interactions were detected for serum mineral concentrations (P ≥ 0.07) except for P (P = 0.001). Results of the present study showed that dietary vitamin E and selenium have synergistic effects, and that supplementing a combination of dietary vitamin E (250 mg) and selenium (0.2 mg) positively influences some blood parameters that may positively influence the performance of Japanese quails under heat stress. J. Trace Elem. Exp. Med. 16:95–104, 2003. © 2003 Wiley‐Liss, Inc.

Effects of oscillating dietary protein on ruminal fermentation and site and extent of nutrient digestion in sheep.

Eight cannulated wethers (BW = 52.5 +/- 5.7 kg) were used in a replicated 4 x 4 Latin square designed experiment to evaluate the effects of oscillating dietary protein concentrations on ruminal fermentation, site and extent of digestion, and serum metabolite concentrations. Four treatments consisted of a 13, 15, or 17% CP diet fed daily or a regimen in which dietary CP was oscillated between 13 and 17% on a 48-h basis (ACP). All diets consisted of 65% bromegrass hay (10.5% CP, 61.9% NDF, 37.2% ADF) plus 35% corn-based supplement and were formulated to contain the same amount of degradable intake protein (9.6% of DM) plus additional undegradable intake protein (SoyPLUS, West Central Cooperative, Ralston, IA) to accomplish CP levels above 13%. Each of four experimental periods were 16 d in duration with 12 d for diet adaptation followed by 4 d for sample collection. All wethers were fed at 3.0% of initial BW (DM basis) throughout the experiment, resulting in an average organic matter intake of 1.39 kg/d across treatments. When compared to the 15% CP daily treatment, feeding ACP had no effect (P > or = 0.10) on ruminal or lower tract N, NDF, ADF, or OM digestion. True ruminal OM digestion responded quadratically (P = 0.07) to increasing dietary CP, reaching a maximum of 52.0% of OM intake with the 15% CP treatment. Sheep fed ACP tended to have lower (P = 0.08) ruminal NH3 N concentrations and an overall higher (P = 0.0001) molar proportion of acetate compared to those fed 15% CP daily. Total VFA concentrations were not affected (P > or = 0.45) by increasing dietary CP. Microbial efficiency did not differ (P > or = 0.55); thus, bacterial N flow at the duodenum responded quadratically (P = 0.04) to increasing dietary CP. Nonbacterial N (P = 0.001) and total N (P = 0.01) flows at the duodenum and total tract N digestibility (P < or = 0.04) increased linearly as dietary CP increased. Wethers fed ACP maintained a lower (P = 0.002) serum glucose and lower (P = 0.0006) serum urea N compared to those fed 15% CP daily. Because the CP content of the diet was increased at the expense of corn, the response to increased CP observed in this experiment is most likely due to negative associative effects of supplemental starch on ruminal fermentation and microbial growth. Oscillating the CP content of the diet on a 48-h basis has little effect on digestion or N utilization in sheep compared with feeding the same quantity of protein on a daily basis.

Acute changes in selected serum enzyme and metabolite concentrations in 12- to 14-yr.-old athletes after an all-out 100-m swimming sprint.

The purpose of this study was to investigate the acute effects of an all-out 100-m swimming sprint on changes in serum enzyme and calcium ion concentrations in young (12 to 14 years) male and female swimmers. Changes in serum enzyme concentrations of creatine kinase (CK), lactate dehydrogenase (LDH), glutamic pyruvate transaminase (GPT), glutamic oxaloacetate transaminase (GOT), serum glucose (GL), and calcium ion ((Ca2+) concentrations were measured in 23 elite swimmers (13 boys and 10 girls) before and after a 100-m freestyle all-out sprint. Analysis showed (1) there were significant sex differences in serum CK concentration at baseline (Pretest); (2) significant sex differences in serum CK and LDH concentrations after the 100-m spring; (3) no significant differences in Ca2+ concentration after the 100-m spring; and (4) significant increase in Serum GOT and blood glucose concentrations after the 100-m sprint, suggesting that these might both be useful indicators of anaerobic exercise stress in young swimmers.

Optimal dietary concentration of vitamin E for alleviating the effect of heat stress on performance, thyroid status, ACTH and some serum metabolite and mineral concentrations in broilers

An experiment utilizing Cobb-500 male broilers was conducted to evaluate the effects of vitamin E (d1--to- copheryl acetate) supplementation at various concentrations (0, 62.5, 125, 250, or 500 mg/kg of diet) on performance and serum concentrations of Triiodothyronine (T&lt;sub&gt;3&lt;/sub&gt;), Thyroxin (T&lt;sub&gt;4&lt;/sub&gt;), Adrenocorticotropine Hormone (ACTH), and some metabolites and minerals in broilers reared under heat stress (32&amp;deg;C). One day-old 150 male broilers were randomly assigned to 5 treatment groups, 3 replicates of 10 birds each. The birds received either a basal diet or basal diet supplemented with vitamin E at 62.5, 125, 250, or 500 mg/kg of diet. Increased supplemental vitamin E linearly increased feed intake (P = 0.01), live weight gain (P = 0.01), and improved feed efficiency linearly (P = 0.001). Increasing dietary vitamin E supplementation also resulted in linear increases in serum T&lt;sub&gt;3 &lt;/sub&gt;and T&lt;sub&gt;4&lt;/sub&gt; concentrations (P = 0.01) but, linear decreases in ACTH concentration (P = 0.01). Serum glucose, uric acid, triglycerides, and cholesterol concentrations decreased linearly (P = 0.001) while, protein and albumin concentrations increased linearly (P = 0.001) when dietary vitamin E supplementation increased. Serum activities of Serum Glutamic Oxalate Transaminase (SGOT) and Serum Glutamic Pyruvate Transaminase (SGPT) were not influenced by dietary vitamin E supplementation (P &amp;gt; 0.10). However, serum activity of Alkaline Phosphatase (AP) increased linearly (P = 0.001) with increasing dietary vitamin E supplementation. Increasing dietary vitamin E supplementation also caused linear increases (P = 0.001) in serum concentrations of Ca and P. Results of the present study conclude that a 250 mg/kg of vitamin E provides an optimal performance in broiler chicks reared under heat stress, and vitamin E supplementation at such a level can be considered as a protective management practice in a broiler diet, reducing the negative effects of heat stress.

Effects of vitamin C and vitamin E on lipid peroxidation status, serum hormone, metabolite, and mineral concentrations of Japanese quails reared under heat stress (34 degrees C).

This study was conducted to determine the effects of dietary vitamin C (L-ascorbic acid) and vitamin E (alpha-tocopherol acetate) on lipid peroxidation status measured as MDA and serum triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), as well as some other serum metabolite and mineral concentrations of Japanese quails reared under heat stress (34 degrees C). One hundred-eighty 10-day-old Japanese quails were randomly assigned to six treatment groups, three replicates of 10 birds each. Using a 2 x 3 factorial design, the birds received two levels of vitamin C (100 and 200 mg/kg of diet) or three levels of vitamin E (125, 250, or 500 mg/kg of diet). Greater dietary vitamin E and vitamin C resulted in a greater serum T3, T4, and TSH (p = 0.001), but lower ACTH (p = 0.001) concentrations. Serum concentrations of T4 and TSH increased to a greater extent by increasing dietary vitamin C when greater vitamin E levels were fed (interaction, p = 0.001). Serum glucose, urea, triglycerides, and cholesterol concentrations decreased (p = 0.001), while protein and albumin concentrations increased (p = 0.001) when both dietary vitamin C and vitamin E were increased. Serum activities of SGOT and SGPT were not influenced by dietary vitamin C and vitamin E (p > 0.43). However, serum activity of AP increased (p = 0.001) by increasing both dietary vitamin C and vitamin E. Increasing both dietary vitamin C and vitamin E caused an increase in serum concentrations of Ca, P, K (p = 0.001), Fe, and Zn (p = 0.01) but a decrease in serum concentrations of Na (p = 0.001) and Cu (p = 0.01). Interactions between vitamin C and vitamin E were detected for Ca, P, Na, and K (p = 0.001). Greater dietary vitamin C and vitamin E resulted in a greater serum and liver vitamin E, C, and A (p < or = 0.05), but lower MDA (p = 0.001) concentrations. Results of the present study conclude that supplementing a combination of dietary vitamin C (200 mg) and vitamin E (250-500 mg) offers a good management practice to reduce heat stress-related decreases in performance of Japanese quails.

A simple way to reduce heat stress in laying hens as judged by egg laying, body weight gain and biochemical parameters.

This study was designed to test the effects of feed withdrawal and darkening on the performance, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and some blood serum metabolite and mineral concentrations of laying hens reared at high ambient temperatures ranging from 25 to 35 degrees C. Ninety, 16-week-old hens (Ross Brown) were divided into 3 groups, 30 hens each. The first group was used as control. Hens in the second group (feed withdrawal) were subjected to feed removal from 14:00 to 18:00, and hens in the third group (darkening) were subjected to light restriction from 14:00 to 18:00 using black curtains. Liveweight, feed intake, and egg production were higher (P < 0.01) in the feed withdrawal and darkening groups, particularly in the darkening group, than in the control. Water intake was higher in the control group compared with the feed withdrawal and darkening groups (P < 0.01). T3, T4, and TSH concentrations in the serum were higher (P < 0.01), whereas ACTH serum concentration was lower (P < 0.01) in the feed withdrawal and darkening groups compared with the control. The haematocrit was higher in the feed withdrawal and darkening groups compared with the control (P < 0.01). Darkening and feed withdrawal treatments increased serum glucose, urea-N, uric acid, albumin, triglyceride, cholesterol, Ca, P, Na, and K concentrations, also the activities of amylase and alkaline phosphatase, but did not influence the activities of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). The present study found that feed withdrawal and darkening, particularly darkening, at high temperatures during the summer months offer a good management practice to reduce heat stress related depression in feed intake and egg production in laying hens.

Effect of degree of corn processing on urinary nitrogen composition, serum metabolite and insulin profiles, and performance by finishing steers.

Two experiments were conducted to determine the effect of degree of corn processing on urinary ammonia and urea N concentrations, serum metabolite and insulin concentrations, and feedlot performance of steers. Corn was processed by either dry rolling to .54 kg/L bulk density (DR42; 42 lb/bushel) or steam flaking to a bulk density of .36 or .26 kg/L (28 [SF28] and 20 [SF20] lb/bushel, respectively). Degrees of processing were selected to generate final products with 25, 50, or 75% enzymatically available starch. Available starch, expressed as a percentage of total starch for DR42, SF28, and SF20, averaged 24.5, 56.4, and 81.1% in Exp. 1 and 22.4, 60.1, and 80.1% in Exp. 2. In Exp. 1, 29 steers were housed in individual outdoor pens and adapted to a 90% concentrate diet over 21 d. Whole blood and urine were collected before feeding and at 4 and 8 h after feeding on d 0, 7, 14, 21, 28, 84, and 140. Daily DMI decreased linearly (P < .03) as degree of processing increased, whereas water intake did not differ (P > .42) among treatments. Average daily gain, ADG:DMI, and hot carcass weight responded quadratically (P < .04) to an increasing degree of processing. Urinary ammonia and urea N concentrations were not influenced (P > .30) by degree of processing. Whole blood packed cell volume, serum glucose, creatinine, D(-)-lactate, L(+)-lactate, and lactate dehydrogenase activity did not differ (P > .15) among treatments. For insulin data, ME intake on the day of sample collection was evaluated as a covariate. On d 28, serum insulin (2.49, 2.95, and 1.80+/-.33 ng/mL) responded quadratically (P = .04) as degree of processing increased. Serum insulin did not differ (P = .52) on d 84, whereas insulin (5.77, 7.51, and 4.12+/-.98 ng/mL) responded quadratically (P = .02) on d 140. In Exp. 2,216 steers were blocked by BW into two blocks (18 pens; 12 steers/pen) and assigned to the same treatments used in Exp. 1. Daily DMI and carcass weight responded quadratically (P < .05), whereas ADG and ADG:DMI increased linearly (P < .04) with increasing degree of processing. Results suggest that the degree of corn processing influences serum insulin concentrations of feedlot steers; however, serum metabolites, urinary nitrogen composition, and carcass characteristics were generally not affected by degree of corn processing.

Effect of physiological stage and nutritional management on some serum metabolite concentrations in Assaf ovine breed

Abstract. The Assaf breed represents a small percentage of the total dairy ovine census in the Castilla-León region and there are no studies conducted solely on this breed for understanding their physiology, nutritional requirements, diseases, management and appropiate beeding methods. The aim of the present report is to evaluate and to comment, in field conditions on, the nutritional management developed in a flock of Assaf ewes, studying the effects on energy metabolism during different physiological conditions (Anoestrus, Pregnancy and Lactation). On the other hand, the effect of litter size was also recorded. The study was conducted on thirty-five ewes of the Assaf breed housed in an intensive management system and randomly assigned to experimental and control groups, the latter divided into singles and twins. All the animals were housed in the same environmental conditions, and received the same diet. The metabolic parameters measured were serum glucose, cholesterol, tnglycendes and NEFA. Our results demonstrate that it is important to consider two critical moments: firstly the early pregnancy period, where the administration of a maintenance diet based on low-energy foods (alfalfa hay) is not enough for energy demands, as was shown by the significant decrease in glucose and triglyceride values; and secondly, late pregnancy, where excessive concentrate intake must be avoided in order to prevent future metabolic diseases and obesity. It has been observed that serum glucose and NEFA values are influenced more by nutritional management than by physiological conditions

Correlations between lamb birth weight and the concentrations of hormones and metabolites in the maternal serum during pregnancy

Maternal serum hormones (progesterone, oestradiol, triiodothyronine and cortisol) and blood metabolites (β-hydroxy butyric acid [BHBA] and blood urea nitrogen [BUN]) concentrations at weeks 0, 4, 8, 12, 16 and 20 of pregnancy were measured in 39 pregnant Javanese thin-tail ewes (20 and 19 carrying single and multiple [2–3] foetuses, respectively), and six non-pregnant ewes as controls, to evaluate their correlations with lamb birth weight at parturition. All hormones and metabolites changed with the advance of pregnancy. Regression analyses showed that concentrations of triiodothyronine, cortisol, BHBA, and BUN in the maternal circulation during pregnancy had lower correlations with lamb birth weight at parturition than those of progesterone and oestradiol. Progesterone and oestradiol concentrations in the maternal circulation at week 8 of pregnancy had the greatest correlations with lamb birth weight at parturition. The higher the concentrations of progesterone and oestradiol in the maternal circulation at week 8 of pregnancy, the higher the lamb birth weight at parturition. The results suggested that raising maternal serum progesterone and oestradiol concentrations during early pregnancy in sheep, either by exogenous administration or superovulation, might improve prenatal growth and lamb birth weight.

Measurement of vitamin D and its metabolites (calcidiol and calcitriol) and their clinical significance

The serum concentration of vitamin D will only give information about the recent exposure to either nutritional vitamin D or to recent vitamin D production in the skin. Within hours vitamin D is removed from the circulation and reappears again a few hours later as 25(OH)D. Measurements of vitamin D therefore are not useful to judge the vitamin D status of man. Plasma concentrations of 25-hydroxyvitamin D (25(OH)D) are the best markers of imminent or existing vitamin D deficiency. Suboptimal vitamin D supply (or 25(OH)D plasma concentrations) are observed in most European countries and North America from November to April. Vitamin D substitution is recommended to persons with a serum concentration of 25(OH)D below 50 nmol/L (20 üg/L). Plasma concentrations of 1,25(OH)2D3 (calcitriol) depend mainly on renal function, concentrations of intact PTH and the supply of the organism with calcium and phosphate. High PTH, low calcium and low phosphate supply are the main stimulators of the production of calcitriol. Vitamin D substitution, or if necessary, therapy with active vitamin D metabolites or analogs, e.g. calcitriol or alfacalcidol, are often necessary in hypercalcemic persons with low serum concentrations of calcitriol, e.g. in patients with renal failure. Disorders with low or high vitamin D metabolite concentrations in serum are described in this paper.

Virginiamycin and Caloric Density Effects on Live Performance, Blood Serum Metabolite Concentration, and Carcass Composition of Broilers Reared in Thermoneutral and Cycling Ambient Temperatures

One experiment utilizing Cobb × Cobb male broilers was conducted to evaluate virginiamycin (VM; 0, 15, 20 ppm) and diet caloric density (CD; 2,945, 3,200 AMEn/kg) effects on broiler live performance, blood serum metabolites, and carcass composition. The starter period exposed birds to recommended brooding conditions, whereas from 3 to 7 wk birds were exposed to thermoneutral (TN, 24 C) or cycling temperature (CT, 24 to 35 C) environments (E). During the 21-d starter period, VM levels and high CD increased (P < 0.05) BW gain (G) and gain:feed (G:F) improved (P < 0.05) with 20 ppm VM and high CD. During 3 to 7 wk, CT reduced (P < 0.05) most live performance and carcass variables as well as heat production (HP) and energetic efficiency whereas energy content per gram of tissue increased. The main effect of VM and CD on blood serum constituents was not significant; however, CT decreased (P < 0.05) serum Na, K, Ca, Mg, Fe, albumin, and total protein. Within CT, G increased (P < 0.05) with high CD and with the 15 ppm VM combination, whereas within TN, G was unaffected by CD, but increased (P < 0.05) with the 20 ppm VM and low CD combination compared with the control. High CD increased (P < 0.05) BW, G, carcass weight, dressing percentage, carcass percentage fat, carcass dry matter, carcass energy content per bird, HP, fat, and protein gain but reduced (P < 0.05) carcass percentage protein and energetic efficiency. Carcass weight, breast yield, fat, and protein gains as well as dry matter carcass energy content increased (P < 0.05) with VM compared with controls. The reduced (P < 0.05) calorie intake and HP with concomitant increase (P < 0.05) in calorie gain with 20 ppm VM increased (P < 0.05) caloric efficiency. In summary, the results suggest that VM improves bird performance by reducing HP and that reduced HP during high CT improves body temperature homeostasis.

How to do it. Get patients' consent to enter clinical trials.

Gaining patients' consent to enter clinical trials is essential, but not easy. Giving careful thought to the design of the study itself, information which patients receive, and the use of a signed consent form may all help. To be properly informed, patients need to know something about their condition, the proposed study, and alternative options. The type and amount of information will vary and investigators need to judge the level appropriate for each person. Patients should understand that taking part in a clinical trial is voluntary and that their decision will not affect the quality of care they receive. The process of obtaining consent requires time and good communication. Working with young, elderly, or mentally impaired patients, or those particularly vulnerable to coercion, requires special sensitivity to the potential dangers.

Feed Access Effects on Serum Metabolites of Hybrid Large White Male Turkeys

A study was conducted utilizing Hybrid Large White male turkeys at 6 wk of age to evaluate feed access effects on various serum metabolite concentrations. Birds deprived of feed for 16 h had lower (P < .05) serum calcium (7.3 vs 8.1 mg/dL), magnesium (2.7 vs 3.2 mEq/L), and triglycerides (45.8 vs 66.6 mg/dL) than birds with ad libitum access to feed. Serum values not impacted (P > .1) by the 16-h feed withdrawal include hematocrit, sodium, potassium, chloride, phosphorus, iron, glucose, total protein, blood urea nitrogen, creatine, lactate dehydrogenase, aspartate aminotransferase, albumin, uric acid, and unsaturated iron-binding capacity.

Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies

purpose: Patients with cobalamin (vitamin B12) deficiency usually lack many of the classic features of severe megaloblastic anemia; because of the low diagnostic specificity of decreased serum cobalamin levels, demonstrating the deficiency unequivocally is often difficult. We examined the sensitivity of measuring serum concentrations of methylmalonic acid and total homocysteine for diagnosing patients with clear-cut cobalamin deficiency and compared the results with those of patients with clear-cut folate deficiency. patients and methods: Serum metabolites were measured for all patients seen from 1982 to 1989 at two university hospitals who met the criteria for cobalamin and folate deficiency states and for such patients seen from 1968 to 1981 from whom stored sera were available. In all, 406 patients had 434 episodes of cobalamin deficiency and 119 patients had 123 episodes of folate deficiency. Criteria for deficiency states included serum vitamin levels, hematologic and neurologic findings, and responses to therapy. Responses were documented in 97% of cobalamin-deficient patients and 76% of folate-deficient patients. Metabolite levels were measured by modified techniques using capillary-gas chromatography and mass spectrometry. results: Most of the cobalamin-deficient patients had underlying pernicious anemia; two thirds were blacks or Latinos. Hematocrits were normal in 28% and mean cell volumes in 17%. Of the 434 episodes of cobalamin deficiency, 98.4% of serum methylmalonic acid levels and 95.9% of serum homocysteine levels were elevated (greater than 3 standard deviations above the mean in normal subjects). Only one patient had normal levels of both metabolites. Serum homocysteine levels were increased in 91% of the 123 episodes of folate deficiency. Methylmalonic acid was elevated in 12.2% of the folate-deficient patients; in all but one, the elevation was attributable to renal insufficiency or hypovolemia. conclusions: For the cobalamin-deficient patients, measuring serum metabolite concentrations proved to be a highly sensitive test of deficiency. We conclude that normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.

Itraconazole Affects Single‐Dose Terfenadine Pharmacokinetics and Cardiac Repolarization Pharmacodynamics

The object of this study was to examine prospectively the effects of itraconazole on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics (QTc intervals) of single-dose terfenadine in six healthy volunteers. It was designed as a prospective cohort study with each subject serving as his own control, set in an outpatient cardiology clinic. The participants were six healthy volunteers (two men, four women; ages 24-35) not taking any prescription or over-the-counter medications. Single-dose terfenadine administration (120 mg) was accompanied by pharmacokinetic profiles and serial determination of the QTc interval for 12 hours. The subjects then began daily oral itraconazole (200 mg each morning) for 7 days. Repeat pharmacokinetic and pharmacodynamic determinations were made after administration of a second dose (120 mg) of terfenadine while receiving itraconazole. The main outcome measures were terfenadine and acid metabolite serum concentrations; corrected QT intervals as determined by 12-lead electrocardiogram (ECG); and presence or absence of late potentials as determined by signal-averaged ECGs over 150 cardiac cycles. There were significant changes in the pharmacokinetic parameters of acid metabolite after treatment with itraconazole. All subjects had detectable levels of unmetabolized terfenadine after addition of itraconazole, which was associated with QT prolongation. There was no evidence of late depolarization as manifested by an increase in QRS duration found using signal-averaged electrocardiography. Itraconazole influences the metabolism of terfenadine in normal volunteers and results in the accumulation of unmetabolized parent drug associated with altered cardiac repolarization. This drug combination should be avoided.

Dietary Chromium Supplementation with or without Somatotropin Treatment Alters Serum Hormones and Metabolites in Growing Pigs without Affecting Growth Performance

Twenty-four castrated male pigs were used in a 2 x 2 treatment array to determine the main effects of and interactions between dietary chromium supplementation and pituitary porcine somatotropin (ppST) administration on growth performance and serum hormone and metabolite concentrations. The treatments were 1) control (basal diet); 2) chromium (basal diet+300 micrograms/kg diet added trivalent chromium as chromium picolinate); 3) ppST (100 micrograms/(kg body wt.d); and 4) chromium+ppST. Treatments were administered when pigs weighed between 30 and 60 kg. Blood was collected when pigs weighted 45 and 60 kg. All pigs treated with ppST exhibited improvements in growth performance (P < 0.05). Pigs given chromium showed no improvements in growth rate, feed efficiency or composition of gain. Measurements at 60 kg body weight revealed that ppST increased the cholesterol:HDL cholesterol ratio (P < 0.05). Chromium lowered serum insulin and glucose concentrations relative to controls (P < 0.05) and normalized the increase in glucose and insulin resulting from ppST treatment. No ppST x chromium interactions were noted, suggesting these changes in glucose and insulin metabolism are exerted through different mechanisms. These results indicate that chromium does not affect growth performance of young growing pigs. Chromium does normalize altered hormone and metabolite concentrations resulting from ppST treatment.

Terfenadine-Ketoconazole Interaction

To examine prospectively the effects of ketoconazole on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics (corrected QT intervals) of terfenadine in men and women. Prospective cohort study with each subject serving as his or her own control. Outpatient cardiology clinic and inpatient telemetry unit for monitoring period. Six healthy volunteers (four men and two women, aged 24 to 35 years) not taking any prescription or over-the-counter medications. After achieving a steady state while taking terfenadine (60 mg every 12 hours for 7 days), daily concomitant oral ketoconazole (200 mg every 12 hours) was added to the subjects' regimen. Pharmacokinetic profiles were obtained while subjects were taking terfenadine alone and after the addition of ketoconazole. Electrocardiograms were obtained at baseline, after 1 week of taking terfenadine alone, and at the time of the second pharmacokinetic profile after the addition of ketoconazole to the regimen. Terfenadine and its acid metabolite serum concentrations and corrected QT intervals. All subjects had detectable levels of unmetabolized terfenadine after the addition of ketoconazole, which was associated with QT prolongation. Only two of the six subjects could complete the entire course of ketoconazole coadministration. Four subjects received a shortened duration of ketoconazole therapy because of significant electrocardiographic repolarization abnormalities. There was a significant change in the area under the curve of the acid metabolite of terfenadine after the addition of ketoconazole administration. Ketoconazole alters the metabolism of terfenadine in normal men and women and results in the accumulation of unmetabolized parent drug, which is associated with significant prolongation of the corrected QT interval. This drug combination should be avoided.

The 10,11-Epoxide-10,11-diol Pathway of Carbamazepine in Early Pregnancy in Maternal Serum, Urine, and Amniotic Fluid

Epoxide metabolites of carbamazepine (CBZ) have been suggested to play a role in the occurrence of congenital malformations observed in infants exposed to CBZ. We have investigated the 10,11-epoxide-10,11-diol pathway of CBZ in pregnant epileptic patients receiving CBZ alone or in combination with other antiepileptic drugs in relation to the outcome of pregnancy in a prospective manner. The women were referred to our clinic before 16 weeks of gestation for prenatal diagnosis of fetal malformations, including neural tube defects, by ultrasound and amniocentesis. The availability of amniotic fluid samples enabled us to determine to what extent CBZ and its main metabolites reached the amniotic fluid. In 100 pregnancies with first trimester CBZ exposure (including 7 with malformed outcome), parent drug and metabolite concentrations in maternal serum were evaluated. CBZ-10,11-epoxide concentrations increased with increasing dose. Comedication with phenobarbital led to lower 10,11-epoxide concentrations in maternal serum and a higher percentage of the dose recovered in urine as 10,11-diol. Valproate comedication led to slightly higher 10,11-epoxide concentrations in maternal serum, in combination with lower CBZ concentrations and a lower percentage of the dose recovered in the urine as 10,11-diol. In amniotic fluid, concentrations of CBZ and its main metabolites in most patients were 2 to 2.5 times higher than the free concentrations in maternal serum. Metabolites and parent drug concentrations in amniotic fluid correlated with their free concentration in maternal serum, but stronger with each other in amniotic fluid. No significant differences in levels of CBZ and its metabolites were observed between pregnancies with normal and malformed outcome.

A note on the influence of oestradiol-17β implants on serum hormone and metabolite concentrations in response to an epinephrine challenge in lambs

Eight wether lambs were used to determine effects of an oestradiol-17β (E2β) implant on metabolic responses to an epinephrine challenge. Blood was sampled before and after an epinephrine challenge, on days 0 and 22 of E2p implantation.Oestradiol-17 ft implants increased pre-injection (basal) serum insulin (INS), growth hormone and free fatty acids (FFA), and decreased basal serum urea nitrogen. After 21 days of E2Pimplantation, total concentrations of FFA decreased and INS increased in response to the epinephrine challenge compared with pre-implantation values. It is concluded that E2/3 implants alter metabolic responses to an epinephrine challenge in wether lambs.

Serum hormone and metabolite concentrations in fasted young bulls and steers

The effect of dietary energy restriction on serum insulin, insulin-like growth factor I (IGF-I), growth hormone, (GH), cortisol, plasma urea nitrogen (PUN) and nonesterified fatty acid (NEFA) concentrations was examined. Angus bulls and steers (10 mo) were allotted to two groups of 12 animals and assigned a treatment order. In a switchback design, animals in order 1 were fed a high grain diet, then fasted, while order 2 animals were fasted, and then fed. Animals were allowed 60 hr to acclimate between treatments. Serum and plasma were obtained at 20 min intervals and 60 min, respectively, for 6 hr after feeding and for the last 6 hr of a 30 hr fast. Serum was assayed for insulin, IGF-I, GH, and cortisol (total and free). Plasma was assayed for PUN and NEFA. Mean insulin (ng/ml) differed between fed (.95 ± .08) and fasted (.26 ± .08) animals (P<01). Both mean total and free cortisol (ng/ml) were lower in fed (11.48 ± .99) (1.06 ± .12) than in fasted (17.10 ± .93) (1.62 ± .12) animals, respectively (P<.01). Animals in order 1 differed in mean IGF-I (ng/ml) between fed (199.0 ± 8.0) and fasted (116.5 ± 7.2) treatments (P<.01). Mean IGF-I for animals in order 2 was 146.7 ± 7.2 in fed and 213.9 ± 7.2 in fasted animals (P<.01). Mean GH did not differ between treatments. Mean PUN and NEFA were higher in fasted than in fed animals (P<.01). Except for % free cortisol (P<.05), the hormones did not differ between bulls and steers. The changes in serum hormones and metabolites may reflect an alteration in metabolism which favors muscle and adipose tissue growth during the fed state, and mobilization of energy substrates during the fasted state.